Cardiac arrhythmias and antiarrhythmic drugs

The sinoatrial node normally leads because it reaches threshold first, at 70 to 80 per minute, faster than the atrioventricular junction (40 to 60) or the Purkinje system (20 to 40). Arrhythmias arise when that order is disturbed. Enhanced automaticity raises the slope of diastolic depolarisation in the sinus node or a latent pacemaker, through sympathetic stimulation, hypoxia, hypokalaemia, stretch or ischaemia, so an ectopic focus outruns the sinus node; conversely, if the sinus node slows or fails, a lower pacemaker escapes at its own slower rate, which is a protective rhythm and not to be suppressed. Triggered activity comes from afterdepolarisations: early afterdepolarisations occur during phase 2 or 3 when repolarisation is prolonged, as in a long QT from drugs, hypokalaemia or a channelopathy, and generate torsades de pointes; delayed afterdepolarisations occur after repolarisation when the cell is overloaded with calcium, as in digitalis toxicity, catecholamine excess or ischaemia, and generate ectopic beats and tachycardia. Re-entry is the commonest mechanism of sustained arrhythmia. It needs a circuit of two functionally different pathways around an obstacle such as a scar, an accessory bundle or a region of ischaemia; one pathway must block the impulse in one direction only, and conduction around the circuit must be slow enough, or the refractory period short enough, that the tissue at the start of the loop has recovered by the time the impulse returns. The impulse then circles indefinitely, driving the chamber faster than the sinus node. This explains atrial flutter (a large circuit in the right atrium), atrioventricular nodal re-entrant tachycardia (fast and slow pathways in the node), atrioventricular re-entrant tachycardia through an accessory bundle as in Wolff-Parkinson-White syndrome, and ventricular tachycardia around the border of an infarct scar. It also explains the two ways to stop such an arrhythmia: slow conduction until the circuit fails, or prolong refractoriness so the returning impulse meets unexcitable tissue.

Read every strip in the same order: rate, regularity, P waves, PR interval, QRS width, and whether each P belongs to a QRS. Sinus tachycardia is a normal complex at over 100 per minute with a P before every QRS, a response to fever, pain, hypovolaemia, anaemia, thyrotoxicosis or catecholamines, and is treated by treating the cause. Atrial premature beats are early narrow complexes preceded by an abnormal P, usually benign. Atrial flutter is a re-entrant circuit at about 300 per minute with saw-tooth flutter waves, conducted to the ventricles in a fixed ratio, most often 2:1, giving a regular rate near 150. Atrial fibrillation replaces P waves with a chaotic baseline and gives an irregularly irregular ventricular response; the loss of atrial contraction reduces cardiac output by up to a fifth, stasis in the left atrial appendage forms thrombus, and embolic stroke is the main hazard, which is why rate or rhythm control is combined with anticoagulation. Paroxysmal supraventricular tachycardia is a regular narrow-complex tachycardia at 150 to 250 per minute, usually re-entrant in or near the atrioventricular node, and often terminated by vagal manoeuvres or adenosine, which transiently blocks the node. In Wolff-Parkinson-White syndrome an accessory bundle bypasses the node, producing a short PR interval and a slurred delta wave at rest and re-entrant tachycardia in attacks; atrioventricular nodal blockers are dangerous if atrial fibrillation conducts down the accessory pathway. Ventricular premature beats are wide, early and not preceded by a P, with a compensatory pause; frequent beats in the ischaemic heart warn of worse. Ventricular tachycardia is three or more consecutive ventricular beats at over 100 per minute with a wide QRS and atrioventricular dissociation; it compromises filling and may degenerate. Ventricular fibrillation is chaotic, ineffective ventricular activity with no recognisable complexes and no output: it is cardiac arrest, and only immediate defibrillation restores a rhythm.

Block is failure of conduction, graded by how much of it fails. First-degree block is a PR interval longer than 0.20 seconds with every P conducted: the impulse is delayed in the atrioventricular node but none is lost, and it is often benign or drug-induced. Second-degree block drops beats. In Mobitz type I (Wenckebach) the PR interval lengthens progressively until a P wave is not conducted and the cycle repeats; the lesion is in the node itself, it is often vagal or drug-related, and it rarely progresses. In Mobitz type II the PR interval is constant and a P wave suddenly fails to conduct; the lesion is below the node in the His-Purkinje system, the escape rhythm is unreliable, and it may progress without warning to complete block, so it needs pacing. In third-degree block no impulse reaches the ventricles: P waves and QRS complexes are each regular but unrelated, the atrial rate is faster than the ventricular, and a junctional escape at 40 to 60 with a narrow QRS or a ventricular escape at 20 to 40 with a wide QRS sustains life; the patient may faint (Stokes-Adams attack) and needs a pacemaker. Causes of block include ischaemia, especially inferior infarction affecting the nodal branch of the right coronary artery, fibrosis of the conduction system in the elderly, myocarditis, rheumatic fever, drugs such as digoxin, beta-blockers, verapamil and diltiazem, and raised vagal tone in athletes. Bundle branch block is failure in one of the two branches: the ventricle on that side is depolarised late and through muscle, so the QRS widens beyond 0.12 seconds and changes shape, with an rSR pattern in V1 in right bundle branch block and a broad notched R in V6 in left bundle branch block. Right bundle branch block may be normal; new left bundle branch block with chest pain is treated as an acute coronary occlusion.

The Vaughan Williams classification groups drugs by the current they block. Class I drugs block the fast sodium channel, slowing phase 0 and therefore conduction, and are subdivided by their effect on repolarisation. Class Ia (quinidine, procainamide, disopyramide) slows conduction moderately and prolongs the action potential and refractory period; it is used for atrial and ventricular arrhythmias but prolongs the QT and can cause torsades de pointes, and each drug has its own toxicity: quinidine causes cinchonism (tinnitus, headache, visual disturbance), diarrhoea and thrombocytopenia and raises digoxin levels; procainamide causes a lupus-like syndrome with long use and agranulocytosis; disopyramide has strong antimuscarinic effects and depresses contractility. Class Ib (lidocaine, mexiletine) binds inactivated channels and dissociates quickly, so it acts mainly on depolarised, ischaemic or rapidly firing ventricular tissue, shortens the action potential and has little effect on normal myocardium or on the ECG; lidocaine is given intravenously for ventricular arrhythmias in ischaemia and has central toxicity (paraesthesia, tremor, confusion, seizures) and is useless in atrial arrhythmias. Class Ic (flecainide, propafenone) blocks strongly with slow dissociation, markedly slows conduction with little effect on repolarisation, and is effective in supraventricular arrhythmias and in maintaining sinus rhythm, but it is proarrhythmic in structural heart disease, where it increased mortality after infarction in the CAST trial, so it is restricted to hearts without ischaemia or scar. Class II drugs are the beta-blockers (propranolol, metoprolol, esmolol). By removing sympathetic stimulation they slow the diastolic depolarisation of the sinoatrial node and slow and prolong refractoriness in the atrioventricular node, so they control the ventricular rate in atrial fibrillation and flutter, terminate or prevent nodal re-entrant tachycardia, suppress the arrhythmias of ischaemia and catecholamine excess, and are among the few antiarrhythmics shown to reduce mortality after infarction. Their adverse effects are bradycardia, block, depressed contractility, bronchospasm, fatigue and masking of hypoglycaemia, and abrupt withdrawal provokes rebound ischaemia.

Class III drugs block potassium channels, prolonging repolarisation and the refractory period without slowing conduction much, so they interrupt re-entry by making the tissue ahead of the impulse unexcitable. Amiodarone is the most used and the least typical: it blocks potassium, sodium and calcium channels and beta receptors, is effective in almost every arrhythmia, and is one of the few safe in structural heart disease and heart failure, but it has a half-life of weeks and a long list of toxicities, pulmonary fibrosis, hepatitis, thyroid dysfunction in both directions because of its iodine content, corneal microdeposits, blue-grey skin pigmentation, photosensitivity and neuropathy, so patients need thyroid, liver and lung monitoring. Sotalol combines class III action with beta-blockade; dofetilide and ibutilide are used for atrial fibrillation. The class risk is QT prolongation and torsades de pointes, least with amiodarone. Class IV drugs are the non-dihydropyridine calcium channel blockers verapamil and diltiazem, which block the L-type channels that carry the upstroke in the sinoatrial and atrioventricular nodes; they slow the rate, prolong nodal refractoriness and are used to control the ventricular rate in atrial fibrillation and flutter and to terminate nodal re-entrant tachycardia, with the cautions of bradycardia, block, hypotension and negative inotropy, and they must be avoided in heart failure, in wide-complex tachycardia of uncertain origin and in Wolff-Parkinson-White syndrome with atrial fibrillation. Outside the classification, adenosine given as a rapid intravenous bolus opens potassium channels and blocks the atrioventricular node for a few seconds, terminating nodal re-entrant tachycardia and unmasking flutter waves, with a half-life under ten seconds and transient flushing, chest tightness and a sense of doom. Digoxin slows the ventricular rate in atrial fibrillation through vagal stimulation, useful when there is also heart failure. Magnesium is the treatment of torsades de pointes and of digitalis-induced arrhythmia. Every antiarrhythmic drug can cause arrhythmia, because the properties that interrupt a circuit, slowed conduction and altered refractoriness, can also create one; this is why drugs are chosen for the arrhythmia and the heart together, why electrophysiological ablation and implantable defibrillators have replaced long-term drug therapy for many patients, and why a drug that suppresses ectopic beats does not necessarily prolong life.